Title

Authors

Date of Completion

Spring 5-1-2014

Thesis Advisor(s)

John D. Salamone

Honors Major

Psychology

Disciplines

Biological Psychology | Other Psychiatry and Psychology

Abstract

Patients with depression, schizophrenia, and other related disorders often show effort-related motivational symptoms such as anergia, psychomotor slowing, lassitude, and fatigue. Several studies have indicated that dopamine (DA) within the nucleus accumbens (NAc) is involved in the regulation of effort-related behavior. Interference with NAc DA alters response allocation in effort related choice procedures, biasing animals towards the alterative that can be obtained with minimal effort. Previous studies have shown that administration of the vesicular monoamine transporter-2 (VMAT-2) inhibitor tetrabenazine (TBZ) shifts behavior in rats responding on the FR5/chow choice procedure causing a decrease in lever pressing and a compensatory increase in chow consumption. By inhibiting VMAT-2, TBZ affects monoamine storage, but studies indicate that the greatest effects are on striatal DA. The deficits induced by TBZ can be successful attenuated through co-administration of the adenosine A2A antagonist, MSX-3, and the dopamine (DA) and norepinephrine (NE) reuptake inhibitor, bupropion. While considerable evidence implicates DA systems in effort-related functions, no previous studies have demonstrated the role of NE in effort-related choice behavior. Therefore, the current studies investigated the ability of tricyclic antidepressant desipramine, which blocks NE uptake, to attenuate TBZ induced shifts in choice behavior. Co-administration of desipramine does not successful reverse the shift in behavior induced by TBZ. In fact the highest dose of desipramine further suppressed lever pressing and chow consumption compared to TBZ-treated animals. The results of this study indicate that NE uptake blockade does not reverse the effects of TBZ, which suggests that DA, rather than NE, is the catecholamine that is most closely involved in effort-related decision making.